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miR‐515‐5p controls cancer cell migration through MARK 4 regulation
Author(s) -
Pardo Olivier E,
Castellano Leandro,
Munro Catriona E,
Hu Yili,
Mauri Francesco,
Krell Jonathan,
Lara Romain,
Pinho Filipa G,
Choudhury Thameenah,
Frampton Adam E,
Pellegrino Loredana,
Pshezhetskiy Dmitry,
Wang Yulan,
Waxman Jonathan,
Seckl Michael J,
Stebbing Justin
Publication year - 2016
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201540970
Subject(s) - medicine , cancer , family medicine
Here, we show that miR‐515‐5p inhibits cancer cell migration and metastasis. RNA ‐seq analyses of both oestrogen receptor receptor‐positive and receptor‐negative breast cancer cells overexpressing miR‐515‐5p reveal down‐regulation of NRAS , FZD 4, CDC 42 BPA , PIK 3C2B and MARK 4 mRNA s. We demonstrate that miR‐515‐5p inhibits MARK 4 directly 3′ UTR interaction and that MARK 4 knock‐down mimics the effect of miR‐515‐5p on breast and lung cancer cell migration. MARK 4 overexpression rescues the inhibitory effects of miR‐515‐5p, suggesting miR‐515‐5p mediates this process through MARK 4 down‐regulation. Furthermore, miR‐515‐5p expression is reduced in metastases compared to primary tumours derived from both in vivo xenografts and samples from patients with breast cancer. Conversely, miR‐515‐5p overexpression prevents tumour cell dissemination in a mouse metastatic model. Moreover, high miR‐515‐5p and low MARK 4 expression correlate with increased breast and lung cancer patients' survival, respectively. Taken together, these data demonstrate the importance of miR‐515‐5p/ MARK 4 regulation in cell migration and metastasis across two common cancers.